Search

Microbial contamination of drinking water is a major public health threat worldwide. Some studies have reported unusual findings of microbiological contamination in distilled water produced from solar stills. Not knowing the exact reason for this presence, they attributed it to possible cross contamination. In the complete absence of literature on the transfer of bacteria in solar stills, this research was conducted to investigate whether bacteria in water subjected to low temperature solar desalination finds its way into the effluent as a result of cross contamination or transfer through water vapor. This study looked at how the type of bacteria and the water temperature affected transfer in the absence of solar UV radiation. Simulated distillation experiments performed in darkness were conducted by spiking a pure culture of Escherichia coli or Enterococcus faecalis in tap water and heating it to low temperature ranges similar to those reached in solar stills under real sunlight. Results show that the two types of bacteria tested in the study were transferred with the vapor in a solar still when not exposed to solar UV radiation and that transfer at the 40–45˚C range is significantly higher than transfer at other temperature ranges. Moreover, transfer is independent of bacterial type; however E. faecalis transfer rates are higher than E. coli at the 40–45 and 50–55˚C ranges. While solar desalination can effectively inactivate bacteria in water, there exists a mode of transfer of bacteria in the humid medium of the solar still to the distillate that takes place under suboptimal weather conditions. [ABSTRACT FROM AUTHOR]

Background: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA)., Objective: We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat., Methods: Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels., Results: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50., Conclusions: During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible., Trial Registration Number: ClinicalTrials.gov, NCT06316414., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines., Objective: To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA., Methods: We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach., Results: We identified 3558 records including 14 randomized trials and 7 observational studies. Very low certainty evidence suggested that in infants with IgE-mediated CMA, eHF-CM, compared with AAF, might have higher probability of outgrowing CMA (risk ratio (RR) 2.32; risk difference (RD) 25 more per 100), while showing potentially lower probability of severe vomiting (RR 0.12, 95% CI 0.02 to 0.88; RD 23 fewer per 100, 95% CI 3 to 26) and developing food protein-induced enterocolitis syndrome (FPIES) (RR 0.15, 95% CI 0.03 to 0.82; RD 34 fewer per 100, 95% CI 7 to 39). We also found, however, that eHF-CM might be inferior to AAF in supporting a physiological growth, with respect to both weight (-5.5% from baseline, 95%CI -9.5% to -1.5%) and length (-0.7 z-score change, 95%CI -1.15 to -0.25) (very low certainty). We found similar effects for eHF-CM, compared with AAF, also in non-IgE CMA. When compared with SF, eHF-CM might favor weight gain for IgE CMA infants (0.23 z-score change, 95%CI 0.01 to 0.45), and tolerance acquisition (RR 1.86, 95%CI 1.03 to 3.37; RD 27%, 95%CI 1%-74%) for non-IgE CMA (both at very low certainty of the evidence (CoE)). The comparison of eHF-CM vs. HRF, and HRF vs. SF, showed no difference in effect (very low certainty). For IgE CMA patients, low certainty evidence suggested that adding probiotics ( L. rhamnosus GG, L. casei CRL431 and B. lactis Bb-12) might increase the probability of developing CMA tolerance (RR 2.47, 95%CI 1.03 to 5.93; RD 27%, 95%CI 1%-91%), and reduce the risk of severe wheezing (RR 0.12, 95%CI 0.02 to 0.95; RD -23%, 95%CI -8% to -0.4%). However, in non-IgE CMA infants, the addition of probiotics ( L. rhamnosus GG) showed no significant effect, as supported by low to very low CoE., Conclusions: Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial., Competing Interests: HJS and JLB, on behalf of McMaster University, received a research grant from the World Allergy Organization to conduct this review that was deposited into the university research account. RS participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott, Else, and Nestlé. HS serves as a board member of the International Scientific Association for Probiotics and Prebiotics (ISAPP), an unpaid and voluntary role. They have participated as a clinical investigator, advisory board member, consultant, and speaker for several companies, including Arla, BioGaia, Biocodex, Danone, Dicofarm, Nestlé, NNI, Nutricia, Mead Johnson, and Novalac. YV has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott Nutrition, Alba Health, Arla, Ausnutria, Biogaia, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Pileje, Sanulac, United Pharmaceuticals (Novalac), Yakult, Wyeth. SW is the president of the Canadian Allergy Asthma and Immunology Foundation, and participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Pfizer, Kaleo, Bausch Health, GSK, AZ, Sanofi, CSL Behring, Leo, AbbVie, Takeda, Medexus Pharma, MiravoHealth, BioCryst, ALK, Novartis. They also covered the positions of: BOD Asthma Canada, CHAEN. MS works for Allergy & Anaphylaxis Australis, which receives unrestricted educational grants from infant formula companies. AW works for Allergy UK works with corporate partners including those providing foods for special medical purposes, such as Nutricia/Danone, Abbott, Reckitt Benckiser/Mead Johnson. They have been a speakers for 2 Nutricia symposia, with honoraria being paid to the charity. All other authors declare that they have no relevant conflicts of interest to disclose., (© 2024 The Author(s).)

Purpose of Review: The purpose of this review is to provide an overview of the perspectives regarding precautionary allergen labelling (PAL) of prepackaged foods following the consultation conducted by the Food and Agriculture Organization (FAO) and the WHO., Recent Findings: The FAO/WHO consultation provided a comprehensive assessment of the current status and practices of PAL implementation worldwide. One of the key findings highlighted by the Expert Committee was the need for improvement in existing PAL systems. It was noted that many countries lacked uniformity in PAL practices, leading to inconsistencies in labelling and potentially misleading information for consumers. Furthermore, the consultation emphasized the importance of PAL being risk-based, taking into account both the amount and frequency of unintended allergen presence (UAP) in food products., Summary: The FAO/WHO consultation shed light on various perspectives and challenges associated with PAL of prepackaged foods. Key findings emphasized the need for improvement in existing PAL systems, including the adoption of a risk-based approach, standardized regulations, and enhanced transparency. Moving forward, collaborative efforts between regulatory agencies, food manufacturers, and consumer advocacy groups will be essential in developing effective PAL strategies that prioritize consumer safety and well being., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit., Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA., Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders., Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence., Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable., Competing Interests: The conduction of these guidelines was funded by WAO and the McMaster University GRADE Centre. Direct funding by for-profit companies was not accepted. The guideline panel members received travel reimbursement for attendance at in-person meetings but received no other payments. The funding was also used as salary support for the information scientist running the original searches, and for research assistants and students conducting the systematic reviews. Some members of the method team who contributed to the systematic review conduction participated without remuneration to fulfill requirements of an academic degree or program. COIs of all participants were managed according to WAO policies based on guidance by the National Academy of Medicine2 and GIN3. Before commencing the project, all the participants were asked to disclose any financial and nonfinancial interests relevant to the guidelines by completing the World Health Organization (WHO) declaration of interest forms. An independent and anonymous WAO committee revised the disclosed interests looking for COIs. The revision committee reviewed the forms and deliberated on including panel members aiming to achieve a diversity of expertise and perspectives, while minimizing the inclusion of panel members with the same or similar conflicts. Specifically, the committee placed a high value on addressing conflicts from direct financial interests from for-profit companies related to the guidelines' field. Throughout the guidelines’ development, the members of the panel and method team were asked to update the interest disclosure forms, which were again revised by the WAO committee. At the time of appointment, most of the guideline panel, including one of the guideline panel co-chair (HJS), had no conflicts of interest. The other co-chair (AF) was aware of economic support by for-profit entities provided to WAO in the form of educational grants; therefore, he abstained from voting on all recommendations in the DRACMA guidelines. The method team members deemed to have a real, potential, or perceived conflict of interest related to the topic of a systematic review were excluded from partaking in that review. Likewise, guideline panel members with manageable real, potential, or perceived conflict of interest abstained from voting on recommendations related to that interest, while being still able to provide intellectual input and clinical expertise. The Evidence-to-Decision (EtD) tables for each recommendation list individuals who were excused from voting. One proposed panel member was found with disqualifying competing interests and was excluded from the DRACMA project entirely.S Arasi, S Bahna, A Bognanni, J Brozek, D Chu, L Dahdah, P Dziechciarz, E Galli, R Kamenwa, H Li, A Martelli, R Pawankar, H Schunemann, R Targino, L Terracciano, and A Warner have no conflicts to disclose. Relationships reported related to the submitted work: IJ Anstotegui – Abbott, Amgen, Astra Zeneca, Bayer, Bial, Faes Farma, Hikma, Menarini, Merck, Mundipharma, Roxall, Sanofi, Stallergenes, UCB. A Assa'ad – Aimmune Therapeutics, DBV Technologies, Astella, ABBVIE, Novartis, Sanofi, FARE, NIH and an intellectual property patent licensed to Hoth. R Berni Canani – Ch.Hansen, Danone, DVB, Humana, iHealth, Kraft Heinz, Mead Johnson, Nestlè, Novalac, Nutricia, Sanofi. M Bozzola – Danone. C Dupont – Nestle Health Science, Nestle France, Nutricia, Novalac, Sodilac, Abbott, Danone, and stock ownership at DBV Technologies. M Ebisawa – DBV Technologies, Mylan, ARS Pharmaceuticals, Novartis. A Fiocchi – Abbott, Danone. G Lack – FARE, National Peanut Board (NPB), The Davis Foundation, Action Medical Research, UK Food Standards Agency, Medical Research Council, DBV Technologies, Mission Mighty Me, Novartis, Sanofi-Genyzme, Regeneron, ALK-Abello, Lurie Children's Hospital. A Nowak-Wegrzyn – Nestle, Nutricia, Novartis, Gerber, Aimmune. N Papadopoulos – Novartis, Nutricia, HAL Allergy, Menarini/Faes Farma, Sanofi, Mylan/Meda, Biomay, AstraZeneca, GSK, MSD, ASIT Biotech, Boehringer Ingelheim, Gerolymatos International SA, Capricare. M Said – Nestle, Nutricia, Abbott, Bayer for Anaphylaxis Australia. R Shamir - Abbott, Else, Nestle. J Spergel – DBV Technologies, Regeneron, Sanofi, and Aimmune. H Szajewska – Ausnutria, Cargill, Danone, Else Nutrition, Hipp, Nestle, and Nestle Nutrition Institute. Y Vandenplas – Abbott Nutrition, Biogaia, Biocodex, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Hero, Hypocrata, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Orafti, Phacobel, Phathom Pharmaceuticals, Sari Husada, United Pharmaceuticals (Novalac), Wyeth, Yakult. C Venter – Reckitt Benckiser, Nestle Nutrition Institute, Danone, Abbott Nutrition, Else Nutrition, and Before Brands, DBV Technologies. A Warner - Nutricia/Danone, Abbott, Reckitt Benckiser/Mead Johnson, Nutricia/Danone for Allergy UK. S Waserman – Novartis-basic science work on peanut allergy, Aimmune-peanut OIT trial, Medical Advisor to Food Allergy Canada, and Pfizer, Bausch, Kaleoconsultant for epinephrine autoinjectors. GWK Wong – Nestle, Danone., (© 2024 The Author(s).)

Background: The supply chains of food raw materials have recently been heavily influenced by geopolitical events. Products that came from, or transited through, areas currently in conflict are now preferentially supplied from alternative areas. These changes may entail risks for food safety., Methods: We review the potential allergenicity of botanical impurities, specifically vegetable contaminants, with particular attention to the contamination of vegetable oils. We delve into the diverse types of botanical impurities, their sources, and the associated allergenic potential. Our analysis encompasses an evaluation of the regulatory framework governing botanical impurities in food labeling., Results: Unintended plant-derived contaminants may manifest in raw materials during various stages of food production, processing, or storage, posing a risk of allergic reactions for individuals with established food allergies. Issues may arise from natural occurrence, cross-contamination in the supply chain, and contamination at during production. The food and food service industries are responsible for providing and preparing foods that are safe for people with food allergies: we address the challenges inherent in risk assessment of botanical impurities., Conclusions: The presence of botanical impurities emerges as a significant risk factor for food allergies in the 2020s. We advocate for regulatory authorities to fortify labeling requirements and develop robust risk assessment tools. These measures are necessary to enhance consumer awareness regarding the potential risks posed by these contaminants.

Background: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts., Methods: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry., Results: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation., Conclusions: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background and Aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings., Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022., Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably., Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe., Prospero Registration Number: CRD42021265689., (© 2023 The Authors.)

Background: Children with severe food allergy may present high risk of fatal anaphylaxis and a highly impaired quality of life. Anti IgE-treatment has been shown to be a promising approach as monotherapy for severe allergy to multiple foods. However, very high serum total IgE levels may limit its use.This study aims to assess the efficacy of IgE-selective immunoadsorption (IgE-IA) on total IgE levels and threshold of reactivity to the culprit foods in children with history of severe anaphylaxis due to multiple foods and allergic comorbidities., Methods: In this single-center, prospective, open-label efficacy study we evaluated children with severe asthma, allergy to 2+foods and total IgE levels >2300 kUI/L. To establish the food reactivity threshold, each patient underwent oral food challenges (OFCs) before and after IgE-IA., Results: Five patients (4 males; age, 12.2 ± 5 years, mean ± SD) underwent an average of 3 (range 2-4) sessions of IgE-IA. Each session reduced IgE levels by a mean of 1958.87 kUI/L. After the IgE-IA cycle, serum total IgE dropped from 3948 ± 1652.7 (mean ± SD) to 360.8 ± 71.9 kUI/L (-10.9 folds; p = 0.01). The threshold of reactivity (No Observed Adverse Effect Level, NOAEL) tested at OFCs for the culprit foods (4 baked-milk + 2 baked-egg + 1 lentil + 2 hazelnut + 1 wheat) increased overall from 21.5 (median, IQR 1.5-82.6) protein milligrams to 1115 (837.2-4222.8) milligrams (p < 0.001), ie, up to 51.8 times higher than baseline. 8/10 OFCs were negative after IgE-IA., Conclusions: IgE-IA increased food threshold quickly. It can be considered in well-selected patients with severe food allergies and high IgE-levels especially if otherwise eligible to anti IgE treatment., (© 2023 The Author(s).)

Background: The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children., Methods: We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children., Results: Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds., Conclusions: The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Aims: Allergy prevention strategies have gained significant traction as a means to attenuate the growing burden of allergic diseases over the past decade. As the evidence base for primary prevention of food allergy (FA) and atopic dermatitis (AD) is constantly advancing, clinical practice guideline (CPG) recommendations on interventions for FA and AD prevention vary in quality and consistency among professional organizations. We present a protocol for a systematic review of CPGs on primary prevention of FA and AD., Methods: We will systematically review and appraise all CPGs addressing primary prevention of FA and AD and report our findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases and manual website searches from January 2011 to March 2021 without language or geographical restrictions, and supplemented by author contact, will generate the list of potentially relevant CPGs to screen. Evaluation of the methodological quality, consistency, and global applicability of shortlisted CPGs will be performed by members of the Allergy Prevention Work Group of the World Allergy Organization (WAO) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and AGREE-REX (Recommendations EXcellence). instruments. Guideline contents, consistency, and quality of the recommendations will be summarised in tabular and narrative formats. We aim to present consolidated recommendations from international guidelines of the highest methodological quality and applicability, as determined by AGREE II and AGREE-REX., Dissemination: This systematic review will provide a succinct overview of the quality and consistency of recommendations across all existing CPGs for FA and AD prevention, as well as crucial perspectives on applicability of individual recommendations in different geographical contexts. Results from this systematic review will be reported in a peer-reviewed journal. It will also inform a position statement by WAO to provide a practical framework to guide the development of future guidelines for allergy prevention worldwide., Prospero Registration Number: CRD42021265689., (© 2022 The Author(s).)

Background: Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA)., Objectives: Hypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey-protein formula (eHWF) in CMA children were assessed., Methods: In this prospective, randomized, international, multi-center study (Trial NL3889), 34 children with confirmed CMA (74% IgE-mediated) underwent a double-blind, placebo-controlled food challenge (DBPCFC) with an eHWF developed with non-porcine enzymes, supplemented with prebiotic short-chain galacto- and long-chain fructo-oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7-day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16-weeks follow-up., Results: Of the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE-mediated CMA) completed the DBPCFC and 7-day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow-up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient., Conclusions: The newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability., Trial Registration: Trial NL3889, https://www.trialregister.nl/trial/3889., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects., Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA., Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment., Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence., Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments., (© 2022 The Authors.)

Background: Since the publication of The World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines in 2010, a number of other guidelines, expert opinions, and position papers relating to the management of cow's milk allergy (CMA) have been published. We aimed to systematically review the quality of the guidelines on CMA diagnosis and management in children and/or adults published between 2010 and 2020., Methods: The MEDLINE, EMBASE, ISI Web of Science, World Health Organization Global Index Medicus, and Turning Research into Practice databases as well as website guideline repositories were searched from January 2010 until May 2020. Any clinical practice recommendations and/or guidelines focusing on the diagnosis and management of CMA in children and/or adults developed or endorsed by professional scientific societies or organizations were included. The guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool, a 23-item tool organized within 6 domains and 2 global rating items., Results: We included 12 guidelines; 8 were developed by national and 4 by international organizations. The quality scores for each domain varied: of all domains, the clarity of presentation domain had the highest median score (92%; Q1-Q3 81-100%), whereas rigor of development had the lowest median score (30%; Q1-Q3 15-67%). The median scores (Q1-Q3) for individual domains were as follows: scope and purpose 82% (70-99%), stakeholder involvement 63% (21-79%), rigor of development 30% (15-67%), clarity of presentation 92% (81-100%), applicability 68% (57-75%), and editorial independence 75% (69-100%). The median overall score was 70% (58-89%). Only 1 guideline (from the National Institute for Health and Care Excellence [NICE]) achieved top ratings (100%) in five domains and the overall score. Three guidelines (from the NICE, the British Society for Allergy & Clinical Immunology [BSACI] and WAO) achieved the highest ratings (100%) in at least 3 domains and the overall score., Conclusion: The majority of identified guidelines were of good or very good quality. However, the weakest point was the rigor of development domain, mostly due to unclear description of strengths and limitations of the body of evidence and the procedure for updating the guidelines., Competing Interests: AS has no potential conflict of interest to declare. AH has participated as a speaker for companies manufacturing infant formulas, ie, Danone, Nestle, Nestle Nutrition Institute, Nutricia, and Mead Johnson. MR has participated as a speaker for companies manufacturing infant formulas, ie, Danone, Nestle, Nestle Nutrition Institute, Nutricia, and Mead Johnson. LD have no conflicts of interest to declare. AF reports currently sponsored research by Danone/Nutricia, the Netherlands, Sanofi/Regeneron, U.S.A., Hipp, Germany, Ferrero, Italy. He is on advisory boards of Danone, Stallergenes, France, Menarini, Italy, Abbott, U.S.A., DBV, U.S.A. - France, Novartis, Switzerland, and Hipp. ANW has participated as consultant and/or speaker for companies manufacturing infant formulas, ie, Danone, Nestle, and Nestle Nutrition Institute. RS has participated as consultant and/or speaker for companies manufacturing infant formulas, ie, Abbott, Danone, Else Nutrition, Nestle, Nestle Nutrition Institute. JMS has participated as consultant for Abbott Nutrition and Nutricia. YV has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott Nutrition, Biogaia, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Phathom Pharmaceuticals, United Pharmaceuticals (Novalac), Wyeth. CV has participated as a speaker for companies manufacturing infant formulas, ie, Danone, Nestle, Nestle Nutrition Institute, Nutricia, and Mead Johnson. CV also received grant funding from Reckitt and the National Peanut Board. HS has participated as consultant and/or speaker for companies manufacturing infant formulas, ie, Ausnutria, Cargill, Danone, Else Nutrition, Hipp, Nestle, Nestle Nutrition Institute. WAO DRACMA guideline group: S Arasi, S Bahna, Bognanni, J Brozek, D Chu, L Dahdah, E Galli, R Kamenwa, H Li, A Martelli, R Pawankar, H Schunemann, R Targino, L Terracciano, and A Warner have no conflicts to disclose. Relationships reported related to the submitted work: IJ Anstotegui – Abbott, Amgen, Astra Zeneca, Bayer, Bial, Faes Farma, Hikma, Menarini, Merck, Mundipharma, Roxall, Sanofi, Stallergenes, UCB. A Assa’ad – Aimmune Therapeutics, DBV Technologies, Astella, ABBVIE, Novartis, Sanofi, FARE, NIH and an intellectual property patent licensed to Hoth. R Berni Canani – Ch.Hansen, Danone, DVB, Humana, iHealth, Kraft Heinz, Mead Johnson, Nestlè, Novalac, Nutricia, Sanofi. M Bozzola – Danone C Dupont – Nestle Health Science, Nestle France, Nutricia, Novalac, Sodilac, Abbott, Danone, and stock ownership at DBV Technologies. M Ebisawa – DBV Technologies, Mylan, ARS Pharmaceuticals, Novartis. A Fiocchi – Abbott, Danone. G Lack – FARE, National Peanut Board (NPB), The Davis Foundation, Action Medical Research, UK Food Standards Agency, Medical Research Council, DBV Technologies, Mission Mighty Me, Novartis, Sanofi-Genyzme, Regeneron, ALK-Abello, Lurie Children’s Hospital. A Nowak-Wegrzyn – Nestle, Nutricia, Novartis, Gerber, Aimmune. N Papadopoulos – Novartis, Nutricia, HAL Allergy, Menarini/ Faes Farma, Sanofi, Mylan/Meda, Biomay, AstraZeneca, GSK, MSD, ASIT Biotech, Boehringer Ingelheim, Gerolymatos International SA, Capricare. M Said – Nestle, Nutricia, Abbott, Bayer for Anaphylaxis Australia. J Spergel – DBV Technologies, Regeneron, Sanofi, and Aimmune. H Szajewska – Ausnutria, Cargill, Danone, Else Nutrition, Hipp, Nestle, and Nestle Nutrition Institute. Y Vandenplas – Abbott Nutrition, Biogaia, Biocodex, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Hero, Hypocrata, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Orafti, Phacobel, Phathom Pharmaceuticals, Sari Husada, United Pharmaceuticals (Novalac), Wyeth, Yakult. C Venter – Reckitt Benckiser, Nestle Nutrition Institute, Danone, Abbott Nutrition, Else Nutrition, and Before Brands, DBV Technologies. S Waserman – Novartis-basic science work on peanut allergy, Aimmune-peanut OIT trial, Medical Advisor to Food Allergy Canada, and Pfizer, Bausch, Kaleo consultant for epinephrine autoinjectors. GWK Wong – Nestle, Danone., (© 2021 The Authors.)

Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergens in foods, and can be used to help avoiding unnecessary PAL.

Background: In some countries of the world, peanut allergy represents an important source of anaphylactic reactions. Traditionally treated with the avoidance of responsible allergens, this condition can also be targeted by oral peanut immunotherapy., Methods: In this study, we review the beneficial and side effects of currently available forms of peanut oral immunotherapy (POIT). We report the discussions resulting from the publication of a meta-analysis that brought to light the downsides of oral immunotherapy for peanuts., Results: In some clinical situations, the risk-benefit ratio can favor peanut oral immunotherapy over avoidance. In many other situations, this is not the case. The decision must be based on the values and preferences of clinicians and patients. Those not ready to accept serious adverse effects from POIT are likely to continue the elimination diet; those motivated to achieving desensitization, and prepared to accept serious adverse effects, may choose to undergo POIT., Conclusions: Without being prejudiced against peanut oral immunotherapy, we indicate the possible evolution of treatment for this condition is in a rapidly evolving broader scenario. Among the future options, sublingual immunotherapy, parenteral immunotherapy with modified allergens, transcutaneous immunotherapy, and the use of biologics will become important options., Competing Interests: Dr. Fiocchi reports currently sponsored research by 10.13039/100007773Danone/Nutricia, the Netherlands, 10.13039/100004339Sanofi/Regeneron, U.S.A., Hipp, Germany, Ferrero, Italy. He is on advisory boards of Danone, Stallergenes, France, Menarini, Italy, Abbott, U.S.A., DBV, U.S.A. - France, Novartis, Switzerland, and Hipp. Dr. Mennini is on advisory board of Biogaia, Sweden., (© 2020 The Authors.)

Purpose of Review: The aim of the article is to examine the contributions made in recent years by evidence-based medicine to the understanding, positioning, and use of drugs for the treatment of the main allergic conditions., Recent Findings: Several antiasthmatic drugs have been reappraised for their efficacy characteristics and drug interactions in Cochrane reviews. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been reformulated in evidence-based medicine (EBM) terms in 2017; over these years, new point of care instruments contributed to the approximation of the guidelines to real life by drawing from the patients themselves information that allows to finely modeling the pharmacological suggestions. Last, at the time of the emergence of new drugs for the treatment of peanut allergy, new systematic reviews have helped to focus on the most suitable reference outcomes with the aim to respond promptly and adherently to patients' needs., Summary: EBM has contributed to changes in the GINA guidelines in the last two years. It has been instrumental in translating the ARIA guidelines in real life. It has also contributed to profiling the potential and limitations of oral peanut immunotherapy. In allergy medicine, EBM is a formidable aid for the advancement of knowledge.

Objectives: Infants with cow's milk allergy (CMA) are in need of a substitute formula up to 2 years. The are three requisites for a substitute of milk in CMA: tolerability, nutritional adequacy, and cost-effectiveness. We evaluate here the tolerability of a new amino acid-based infant formula for the management of CMA., Methods: In a phase III/IV prospective, multicentre, open-label, international study, infants and children with immunoglobulin E-mediated CMA were exposed to a diagnostic double-blinded, placebo-controlled food challenge with a new amino acid formula by Blemil Plus Elemental using Neocate as the placebo. If tolerant to it, the study formula was integrated into the patients' usual daily diet for 7 days. Efficacy on day 7 was assessed in terms of symptoms associated with CMA, amount of formula consumed, nutritional and energy intake, and anthropometric data., Results: Thirty children (17 M and 13 F; median age, 1.58; range, 0.08-12.83 years) completed the open challenge and were able to consume the study formula for at least 7 days. No signs or symptoms of allergic reactions were recorded among children assuming either the test or the control formula, with a lower 95% one-sided confidence interval for the proportion of subjects who did not experience allergic reactions above 90%. Sixteen patient under the age of two continued with the optional extension phase., Conclusions: The study formula meets the American Academy of Pediatric criteria for hypoallergenicity and is well tolerated in short-term use. During optional phase, growth of the patients was not hindered by the study formula., (© 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Purpose of Review: In the last years, the interest of the scientific community toward food protein-induced enterocolitis syndrome (FPIES) has grown exponentially. We review here the peculiar characteristics of this syndrome., Recent Findings: The recent publication of the First International Consensus Guidelines allowed a positive interaction between different research groups with the aim of improving the diagnosis and management of patients affected by FPIES., Summary: Several fixed points have been placed on the diagnosis and management, but further studies are needed to clarify the many shadows that still surround different aspects of the syndrome, especially regarding the pathophysiology.

Food allergy (FA) is currently a significant health care problem in the developing world. Widely varying study populations and methodologies, the use of surrogate markers such as self report or hospitalization rates due to anaphylaxis rather than objective methods, limits robust estimation of FA prevalence in low income settings. Also, allergy is under-recognized as a clinical specialty in the developing world which compromises the chance for accurate diagnosis. In this review, most published data on food allergens from developing or low income countries are displayed. The diagnostic challenges and limitations of treatment options are discussed. It seems that FA is an under-appreciated health care issue in the developing world, and accurate determination of its burden in low-income settings represents an important unmet need. Multicenter surveillance studies, using standardized methodologies, are, therefore, needed to reveal the true extent of the problem and provide epidemiological clues for prevention. Preventive strategies should be tailored to fit local circumstances in different geographic regions. In addition, studying the gene environment interactions and impact of early life microbiota on the expression of FA in developing communities would be worthwhile. Efforts and resources should be directed toward public health education and training of health care providers dealing with food allergic patients., Competing Interests: The authors report no competing interests to declare in relevance to the article., (© 2019 The Authors.)

Background: The effects of omalizumab on food allergy thresholds have been little studied., Objective: To assess the real-life effects of omalizumab on food threshold tolerability in children treated for severe asthma., Methods: In this observational, real-life, efficacy study, we reviewed the food allergen thresholds of patients with severe asthma, as well as their immediate reactions to 2+ foods before and after a 4-month treatment with omalizumab. We also evaluated their control of asthma and their quality of life, as measured by Pediatric Quality of Life Inventory (PedsQL)., Results: Fifteen children, allergic to 37 foods, were evaluated. Omalizumab induced an increase in the allergen threshold for milk, egg, wheat, and hazelnut from a mean 1012.6 ± 1464.5 mg protein to 8727 ± 6463.3 eliciting dose (P < .001). A total of 70.4% of subjects tolerated the complete challenge dose after 4 months of treatment with omalizumab. These foods were reintroduced in the patients' diet without the need for any oral immunotherapy procedures. The remaining foods were partially tolerated. The number of reactions to the unintended ingestion of allergenic foods over 4 months dropped from 47 to 2. The PedsQL increased from 61 ± 5.32 to 87 ± 7.33 (parental judgment; P < .001) and from 65 ± 7.39 to 90 ± 4.54 (patients' judgment; P < .001). The mean cost of omalizumab was €1311.63 per month., Conclusions: During treatment with omalizumab for severe uncontrolled asthma, the food allergen threshold increases to 8.6 times its original value. The quality of life of patients also increased, due to a better asthma control and a reduction in dietary restrictions. The cost/benefit ratio of such treatment for selected cases of food allergy remains to be evaluated., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice., Recent Findings: DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable., Summary: DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.